Myofiber-specific TEAD1 overexpression drives satellite cell hyperplasia and counters pathological effects of dystrophin deficiency
When unperturbed, somatic stem cells are poised to affect immediate tissue restoration upon trauma. Yet, little is known regarding the mechanistic basis controlling initial and homeostatic ‘scaling’ of stem cell pool sizes relative to their target tissues for effective regeneration. Here, we show th...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/15461 |
| _version_ | 1811236983185342464 |
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| author | Sheryl Southard Ju-Ryoung Kim SiewHui Low Richard W Tsika Christoph Lepper |
| author_facet | Sheryl Southard Ju-Ryoung Kim SiewHui Low Richard W Tsika Christoph Lepper |
| author_sort | Sheryl Southard |
| collection | DOAJ |
| description | When unperturbed, somatic stem cells are poised to affect immediate tissue restoration upon trauma. Yet, little is known regarding the mechanistic basis controlling initial and homeostatic ‘scaling’ of stem cell pool sizes relative to their target tissues for effective regeneration. Here, we show that TEAD1-expressing skeletal muscle of transgenic mice features a dramatic hyperplasia of muscle stem cells (i.e. satellite cells, SCs) but surprisingly without affecting muscle tissue size. Super-numeral SCs attain a ‘normal’ quiescent state, accelerate regeneration, and maintain regenerative capacity over several injury-induced regeneration bouts. In dystrophic muscle, the TEAD1 transgene also ameliorated the pathology. We further demonstrate that hyperplastic SCs accumulate non-cell-autonomously via signal(s) from the TEAD1-expressing myofiber, suggesting that myofiber-specific TEAD1 overexpression activates a physiological signaling pathway(s) that determines initial and homeostatic SC pool size. We propose that TEAD1 and its downstream effectors are medically relevant targets for enhancing muscle regeneration and ameliorating muscle pathology. |
| first_indexed | 2024-04-12T12:18:07Z |
| format | Article |
| id | doaj.art-bc22a392f4d8417d9e13388c12dfdd81 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:18:07Z |
| publishDate | 2016-10-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-bc22a392f4d8417d9e13388c12dfdd812022-12-22T03:33:23ZengeLife Sciences Publications LtdeLife2050-084X2016-10-01510.7554/eLife.15461Myofiber-specific TEAD1 overexpression drives satellite cell hyperplasia and counters pathological effects of dystrophin deficiencySheryl Southard0Ju-Ryoung Kim1SiewHui Low2Richard W Tsika3Christoph Lepper4https://orcid.org/0000-0002-6466-0820Department of Embryology, Carnegie Institution for Science, Baltimore, United StatesDepartment of Biochemistry, University of Missouri, Columbia, United States; School of Medicine, University of Missouri, Columbia, United States; Department of Biomedical Sciences, University of Missouri, Columbia, United States; College of Veterinary Medicine, University of Missouri, Columbia, United StatesDepartment of Embryology, Carnegie Institution for Science, Baltimore, United StatesDepartment of Biochemistry, University of Missouri, Columbia, United States; School of Medicine, University of Missouri, Columbia, United States; Department of Biomedical Sciences, University of Missouri, Columbia, United States; College of Veterinary Medicine, University of Missouri, Columbia, United StatesDepartment of Embryology, Carnegie Institution for Science, Baltimore, United StatesWhen unperturbed, somatic stem cells are poised to affect immediate tissue restoration upon trauma. Yet, little is known regarding the mechanistic basis controlling initial and homeostatic ‘scaling’ of stem cell pool sizes relative to their target tissues for effective regeneration. Here, we show that TEAD1-expressing skeletal muscle of transgenic mice features a dramatic hyperplasia of muscle stem cells (i.e. satellite cells, SCs) but surprisingly without affecting muscle tissue size. Super-numeral SCs attain a ‘normal’ quiescent state, accelerate regeneration, and maintain regenerative capacity over several injury-induced regeneration bouts. In dystrophic muscle, the TEAD1 transgene also ameliorated the pathology. We further demonstrate that hyperplastic SCs accumulate non-cell-autonomously via signal(s) from the TEAD1-expressing myofiber, suggesting that myofiber-specific TEAD1 overexpression activates a physiological signaling pathway(s) that determines initial and homeostatic SC pool size. We propose that TEAD1 and its downstream effectors are medically relevant targets for enhancing muscle regeneration and ameliorating muscle pathology.https://elifesciences.org/articles/15461skeletal musclesatellite cellregenerationmuscular dystrophy |
| spellingShingle | Sheryl Southard Ju-Ryoung Kim SiewHui Low Richard W Tsika Christoph Lepper Myofiber-specific TEAD1 overexpression drives satellite cell hyperplasia and counters pathological effects of dystrophin deficiency eLife skeletal muscle satellite cell regeneration muscular dystrophy |
| title | Myofiber-specific TEAD1 overexpression drives satellite cell hyperplasia and counters pathological effects of dystrophin deficiency |
| title_full | Myofiber-specific TEAD1 overexpression drives satellite cell hyperplasia and counters pathological effects of dystrophin deficiency |
| title_fullStr | Myofiber-specific TEAD1 overexpression drives satellite cell hyperplasia and counters pathological effects of dystrophin deficiency |
| title_full_unstemmed | Myofiber-specific TEAD1 overexpression drives satellite cell hyperplasia and counters pathological effects of dystrophin deficiency |
| title_short | Myofiber-specific TEAD1 overexpression drives satellite cell hyperplasia and counters pathological effects of dystrophin deficiency |
| title_sort | myofiber specific tead1 overexpression drives satellite cell hyperplasia and counters pathological effects of dystrophin deficiency |
| topic | skeletal muscle satellite cell regeneration muscular dystrophy |
| url | https://elifesciences.org/articles/15461 |
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